Research Papers:

The adaptive immune system promotes initiation of prostate carcinogenesis in a human c-Myc transgenic mouse model

Monique H.M. Melis, Ekaterina Nevedomskaya, Johan van Burgsteden, Bianca Cioni, Hester J.T. van Zeeburg, Ji-Ying Song, John Zevenhoven, Lukas J.A.C Hawinkels, Karin E. de Visser and Andries M. Bergman _

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Oncotarget. 2017; 8:93867-93877. https://doi.org/10.18632/oncotarget.21305

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Monique H.M. Melis1, Ekaterina Nevedomskaya1, Johan van Burgsteden1, Bianca Cioni1, Hester J.T. van Zeeburg1, Ji-Ying Song2, John Zevenhoven1, Lukas J.A.C Hawinkels3, Karin E. de Visser4 and Andries M. Bergman1,5

1Division of Molecular Genetics, Netherlands Cancer Institute, The Netherlands

2Division of Experimental Animal Pathology, Netherlands Cancer Institute, The Netherlands

3Division of Gastroenterology-Hepatology and Molecular Cell biology, Leiden university medical center, (LUMC), Netherlands

4Division of Immunology, Netherlands Cancer Institute, The Netherlands

5Division of Medical Oncology, Netherlands Cancer Institute, The Netherlands

Correspondence to:

Andries M. Bergman, email: [email protected]

Keywords: prostate cancer, GEMM, adaptive immune system

Received: April 07, 2017    Accepted: August 26, 2017    Published: September 28, 2017


Increasing evidence from epidemiological and pathological studies suggests a role of the immune system in the initiation and progression of multiple cancers, including prostate cancer. Reports on the contribution of the adaptive immune system are contradictive, since both suppression and acceleration of disease development have been reported. This study addresses the functional role of lymphocytes in prostate cancer development using a genetically engineered mouse model (GEMM) of human c-Myc driven prostate cancer (Hi-Myc mice) combined with B and T cell deficiency (RAG1-/- mice). From a pre-cancerous stage on, Hi-Myc mice showed higher accumulation of immune cells in their prostates then wild-type mice, of which macrophages were the most abundant. The onset of invasive adenocarcinoma was delayed in Hi-MycRAG1-/- compared to Hi-Myc mice and associated with decreased infiltration of leukocytes into the prostate. In addition, lower levels of the cytokines CXCL2, CCL5 and TGF-β1 were detected in Hi-MycRAG1-/- compared to Hi-Myc mouse prostates. These results from a GEMM of prostate cancer provide new insights into the promoting role of the adaptive immune system in prostate cancer development. Our findings indicate that the endogenous adaptive immune system does not protect against de novo prostate carcinogenesis in Hi-Myc transgenic mice, but rather accelerates the formation of invasive adenocarcinomas. This may have implications for the development of novel treatment strategies.

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